Study On CDH2,LEP,POSTN,TIMP1,VEGFC Expression And 5-FU Sensitivity In Colon Cancer

Objective Drug resistance in colon cancer chemotherapy influences the prognosis in patients with cancer,clinically,there is lack of drug resistance markers.In the current study,using bioinformatics analysis explores the association between gene expression and fluorouracil(5-FU)sensitivity related to provide theoretical foundations for further investigation.Methods In this study,genes related to cancer recurrence and chemotherapy resistance were identified by data mining.Immunohistochemistry(IHC)was performed to test protein expression in human colon cancer tissues.Quantitative real-time PCR(qPCR)analysis was conducted to test messenger RNA expression.Colon cancer cell lines(HCT116 and LoVo)were utilized for toxicity of fluorouracil by CCK8 assay.Cell apoptosis was measured by propidium iodide(PI)staining.Results Here,we identified 602 genes using both "cancer recurrence" and"chemoresistance" terms on the GenCLiP3 website.Gene functional annotation was performed using "DAVID6.8".Then,the 602 genes were enriched by STRING analysis,four high correlation subsets were obtained.In the GEPIA database,we further found that 14 genes(ATM,CDH2,CDKN2A,EPO,LEP,TGFB1,TIMP1,PGR,VEGFC,POSTN,BCL6,CYP19A1,NOTCH3,and XPA)were significantly upregulated in colon cancer and were associated with poor prognosis in patients with colon cancer.In 33 paired human colon cancer tissues,data revealed that eight genes(ATM,CDH2,CDKN2A,LEP,PGR,TIMP1,POSTN,and VEGFC)were significantly upregulated,which was consistent with the results obtained from the dataset,of which five genes(CDH2,LEP,POSTN,TIMP1,and VEGFC)were associated with prognosis in patients with colon cancer.Silencing of these five genes via siRNA transfection significantly enhanced the sensitivity of colon cancer cells to the chemotherapeutic agent 5-fluorouracil(5-FU).Conclusion Overall,our results suggest that the expression of CDH2,LEP,POSTN,TIMP1 and VEGFC genes modulate the chemotherapeutic sensitivity of fluorouracil in colon cancer,which are promising targets for overcoming fluorouracil resistance and potential markers of chemotherapy resistance in colon cancer.